WO2019029561A1 - 自催化双亲混合溶剂中合成1,5,7-三氮杂双环[5.5.0]癸-5-烯的工艺方法 - Google Patents

自催化双亲混合溶剂中合成1,5,7-三氮杂双环[5.5.0]癸-5-烯的工艺方法 Download PDF

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WO2019029561A1
WO2019029561A1 PCT/CN2018/099368 CN2018099368W WO2019029561A1 WO 2019029561 A1 WO2019029561 A1 WO 2019029561A1 CN 2018099368 W CN2018099368 W CN 2018099368W WO 2019029561 A1 WO2019029561 A1 WO 2019029561A1
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tbd
solution
reaction
amine
aminopropyl
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李弘�
张全兴
孙向前
黄伟
江伟
潘丙才
李爱民
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Nanjing University
Nanjing Tech University
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Nanjing Tech University
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/04—Ortho-condensed systems

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  • the invention belongs to the technical field of organic synthesis and relates to a process for synthesizing (1,5,7-triazabicyclo[5.5.0]non-5-ene) in a self-catalyzed amphiphilic mixed solvent.
  • 1,5,7-Triazabicyclo[5.5.0]non-5-ene (commonly known as: bicyclic oxime; English abbreviation: TBD) is an organic strong base that exhibits good catalysis for various organic reactions and polymerizations. effect.
  • CN 103172639A reported a method for synthesizing TBD in the absence of a solvent using bis(3-aminopropyl)amine and hydrazine hydrochloride as starting materials.
  • the problem with this method is that the hydrazine hydrochloride solid reacts with the bis(3-aminopropyl)amine liquid in a heterogeneous manner due to the large difference in polarity between the two reaction materials, and the reaction time is longer. Long, side reactions, product purity is not high, separation is difficult. Finding a suitable amphiphilic reaction solvent system and reacting the two reactants under homogeneous conditions is one of the effective ways to improve the yield and purity of the product TBD.
  • the object of the present invention is to overcome the problems existing in the existing TBD synthesis process, and provide a process for synthesizing (1,5,7-triazabicyclo[5.5.0]non-5-ene) in an autocatalytic amphiphilic mixed solvent. .
  • the process for synthesizing (1,5,7-triazabicyclo[5.5.0]non-5-ene) in the autocatalytic amphiphilic mixed solvent provided by the present invention is bis(3-aminopropyl)amine and sulfonium salt.
  • the acid salt is used as a raw material, and the TBD is synthesized by a self-catalytic method (trace finished TBD as a catalyst) in a hydrophilic-hydrophobic parent mixed solvent.
  • the specific steps are as follows:
  • reaction temperature is maintained at 120-145 ° C, and the hydrazine hydrochloride solution prepared in step (1) is added dropwise into the reaction kettle, and the control is completed within 0.5-1.0 h, and the addition is completed. Continue the reaction after 3.0-4.5h;
  • TBD dichloromethane solution is obtained by removing the methylene chloride by rotary distillation to obtain a white or yellowish solid which is dried in vacuo for 24 to 48 h to obtain product TBD, yield ⁇ 95.0%, purity ⁇ 98.0%.
  • the hydrophilic solvent is specifically one of diethylene glycol and triethylene glycol; and the hydrophobic solvent is specifically one of mesitylene and tetramethylbenzene.
  • the target product has a high yield ( ⁇ 95%) and the product purity is high ( ⁇ 98%).
  • the reaction temperature was maintained at 120 ° C, and the above-mentioned hydrazine hydrochloride diethylene glycol solution was added dropwise into the reaction vessel, and the dropwise addition was completed within 0.5 h after the completion of the dropwise addition, and the reaction was continued for 3.0 h after the completion of the dropwise addition.
  • the solvent was evaporated to give a white solid.
  • the aqueous solution was adjusted to pH 10 by adding sodium hydroxide, and extracted with dichloromethane, and the obtained dichloromethane solution was a TBD dichloromethane solution.
  • TBD dichloromethane solution was obtained by removing the methylene chloride by rotary distillation to give a white or yellowish solid which was dried in vacuo for 48 h to afford product TBD (yield: 95.0%, purity 98.0%).
  • the reaction temperature was maintained at 138 ° C, and the above-mentioned hydrazine hydrochloride triethylene glycol solution was added dropwise into the reaction vessel, and the dropwise addition was completed within 1.0 h after the completion of the dropwise addition, and the reaction was continued for 4.0 h after the completion of the dropwise addition.
  • the solvent was evaporated to give a white solid.
  • the aqueous solution was adjusted to pH 11 by adding sodium hydroxide, and dichloromethane was added for extraction. The obtained dichloromethane solution was a TBD dichloromethane solution.
  • TBD dichloromethane solution was obtained by removing the methylene chloride by rotary distillation to give a white or yellowish solid which was dried in vacuo for 48 h to afford product TBD, yield 97.0%, purity 98.5%.
  • the reaction temperature was maintained at 145 ° C, and the above-mentioned hydrazine hydrochloride diethylene glycol solution was added dropwise into the reaction vessel, and the dropwise addition was controlled within 0.5 h. After the completion of the dropwise addition, the reaction was continued for 4.5 hours. After completion of the reaction, the solvent was evaporated to give a white solid.
  • the aqueous solution was adjusted to pH 12 by adding sodium hydroxide, and extracted with dichloromethane, and the resulting dichloromethane solution was a TBD dichloromethane solution.
  • the obtained TBD dichloromethane solution was obtained by removing the methylene chloride by rotary distillation to give a white or yellowish solid which was dried in vacuo for 48 h to afford product TBD, yield 98.0%, purity 99.0%.
  • the reaction temperature was maintained at 145 ° C, and the above-mentioned hydrazine hydrochloride triethylene glycol solution was added dropwise into the reaction vessel, and the dropwise addition was controlled within 1.0 h. After the completion of the dropwise addition, the reaction was continued for 4.0 h. After completion of the reaction, the solvent was evaporated to give a white solid. After dissolving the TBD hydrochloride in water, the aqueous solution was adjusted to pH 11 by adding sodium hydroxide, and dichloromethane was added for extraction. The obtained dichloromethane solution was a TBD dichloromethane solution.
  • TBD dichloromethane solution was obtained by removing the methylene chloride by rotary distillation to give a white or yellowish solid, which was dried in vacuo for 48 h to afford product TBD (yield 98.5%, purity 99.5%).
  • the reaction temperature was maintained at 138 ° C, and the above-mentioned hydrazine hydrochloride diethylene glycol solution was added dropwise into the reaction vessel, and the dropwise addition was completed within 0.5 h after the completion of the dropwise addition, and the reaction was continued for 4.5 hours after the completion of the dropwise addition.
  • the solvent was evaporated to give a white solid.
  • the aqueous solution was adjusted to pH 10 by adding sodium hydroxide, and extracted with dichloromethane, and the obtained dichloromethane solution was a TBD dichloromethane solution.
  • TBD dichloromethane solution was obtained by removing the methylene chloride by rotary distillation to give a white or yellowish solid which was dried in vacuo for 48 h to afford product TBD (yield 97.6%, purity 98.7%).
  • the reaction temperature was maintained at 120 ° C, and the above-mentioned hydrazine hydrochloride triethylene glycol solution was added dropwise into the reaction vessel, and the dropwise addition was completed within 1.0 h after the completion of the dropwise addition, and the reaction was continued for 3.0 h after the completion of the dropwise addition.
  • the solvent was evaporated to give a white solid.
  • the aqueous solution was adjusted to pH 12 by adding sodium hydroxide, and extracted with dichloromethane, and the resulting dichloromethane solution was a TBD dichloromethane solution.
  • the obtained TBD dichloromethane solution was obtained by removing the methylene chloride by rotary distillation to give a white or yellowish solid, which was dried in vacuo for 24h to give product TBD, yield 95.6%, purity 98.9%.
  • the reaction temperature was maintained at 138 ° C, and the above-mentioned hydrazine hydrochloride diethylene glycol solution was added dropwise into the reaction vessel, and the dropwise addition was completed within 0.5 h after the completion of the dropwise addition, and the reaction was continued for 4.5 hours after the completion of the dropwise addition.
  • the solvent was evaporated to give a white solid.
  • the aqueous solution was adjusted to pH 12 by adding sodium hydroxide, and extracted with dichloromethane, and the resulting dichloromethane solution was a TBD dichloromethane solution.
  • the obtained TBD dichloromethane solution was obtained by removing the methylene chloride by rotary distillation to give a white or yellowish solid, which was dried in vacuo for 24h to give product TBD, yield 98.7%, purity 99.1%.
  • the reaction temperature was maintained at 120 ° C, and the above-mentioned hydrazine hydrochloride triethylene glycol solution was added dropwise into the reaction vessel, and the dropwise addition was controlled within 1.0 h. After the completion of the dropwise addition, the reaction was continued for 4.0 h. After completion of the reaction, the solvent was evaporated to give a white solid.
  • the aqueous solution was adjusted to pH 11 by adding sodium hydroxide, and dichloromethane was added for extraction.
  • the obtained dichloromethane solution was a TBD dichloromethane solution.
  • the obtained TBD dichloromethane solution was obtained by removing the methylene chloride by rotary distillation to give a white or yellowish solid, which was dried in vacuo for 24h to give product TBD, yield 97.3%, purity 99.4%.
  • the reaction temperature was maintained at 145 ° C, and the above-mentioned hydrazine hydrochloride triethylene glycol solution was added dropwise into the reaction vessel, and the dropwise addition was completed within 0.5 h after the completion of the dropwise addition, and the reaction was continued for 3.0 h after the completion of the dropwise addition.
  • the solvent was evaporated to give a white solid.
  • the aqueous solution was adjusted to pH 10 by adding sodium hydroxide, and extracted with dichloromethane, and the obtained dichloromethane solution was a TBD dichloromethane solution.
  • the obtained TBD dichloromethane solution was obtained by removing the methylene chloride by rotary distillation to give a white or yellowish solid, which was dried in vacuo for 24h to give product TBD, yield 99.2%, purity 98.2%.

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  • Organic Chemistry (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

自催化双亲混合溶剂中合成1,5,7-三氮杂双环[5.5.0]癸-5-烯(TBD)的工艺方法。本发明以双(3-氨基丙基)胺和胍盐酸盐为原料，在亲水—疏水性双亲混合溶剂中采用微量(0.001％-0.005％)TBD为催化剂高产率合成TBD的工艺方法。本方法特点：工艺操作简便，目标产物产率高(≥95.0％)，产物纯度高(≥98.0％)。

Description

自催化双亲混合溶剂中合成1,5,7-三氮杂双环[5.5.0]癸-5-烯的工艺方法 技术领域
本发明属于有机合成技术领域，涉及自催化双亲混合溶剂中合成(1,5,7-三氮杂双环[5.5.0]癸-5-烯)的工艺方法。
背景技术
1,5,7-三氮杂双环[5.5.0]癸-5-烯(俗称：双环胍；英文缩写：TBD)是一种有机强碱，对多种有机反应及聚合反应呈现良好的催化作用。
此前，CN 103172639A报道了一种以双(3-氨基丙基)胺和胍盐酸盐为原料，在无溶剂存在的条件下合成TBD的方法。这一方法的问题在于：由于两种反应原料极性具有较大的差异无法互溶，胍盐酸盐固体与双(3-氨基丙基)胺液体以非均相的形式进行反应，反应时间较长、副反应多、产物纯度不高、分离困难。寻找合适的双亲型反应溶剂体系，使两种反应物在均相条件下进行反应是提高产品TBD产率及纯度的有效途径之一。
发明内容
本发明的目的在于克服现有TBD合成工艺存在的问题，提供一种自催化双亲混合溶剂中合成(1,5,7-三氮杂双环[5.5.0]癸-5-烯)的工艺方法。
本发明提供的自催化双亲混合溶剂中合成(1,5,7-三氮杂双环[5.5.0]癸-5-烯)的工艺方法是以双(3-氨基丙基)胺和胍盐酸盐为原料，在亲水—疏水性双亲混合溶剂中，采用自催化法(痕量成品TBD为催化剂)合成TBD，具体步骤如下：
1)将双(3-氨基丙基)胺和胍盐酸盐分别溶于疏水性溶剂和亲水性溶剂中，控制各溶液浓度在1.0-10.0mol/L，控制胍盐酸盐与双(3-氨基丙基)胺的摩尔比为1：(0.8-1.2)；
2)将上述双(3-氨基丙基)胺溶液加入配有回流冷凝器及搅拌设备的反应釜中，随后加入胍盐酸盐摩尔量0.001％-0.005％的TBD作为催化剂；
3)在氩气保护下，维持反应温度在120-145℃，将步骤(1)配制的胍盐酸盐溶液滴加进反应釜中，控制在0.5-1.0h内滴加完毕，滴加完毕后继续反应3.0-4.5h；
4)反应完毕后，旋蒸除去双亲混合溶剂，得到白色固体即为TBD盐酸盐；
5)将TBD盐酸盐用水溶解后，加入氢氧化钠调节水溶液至pH 10-12，加入二氯甲烷萃取，所得二氯甲烷溶液即为TBD二氯甲烷溶液；
6)所得TBD二氯甲烷溶液，通过旋蒸除去二氯甲烷所得白色或微黄色固体经真空干燥24-48h后，即得到产品TBD，产率≥95.0％、纯度≥98.0％。
本发明所述的工艺方法所述亲水—疏水性双亲混合溶剂中，亲水性溶剂具体为二甘醇、三甘醇之一；疏水性溶剂具体为均三甲苯、均四甲苯之一。
本发明的优点和有益效果：
工艺操作简便；
目标产物产率高(≥95％)，产物纯度高(≥98％)。
具体实施方式
实施例1
将100.0g(0.762mol)双(3-氨基丙基)胺溶于均三甲苯，配制成1.0mol/L的溶液；将72.8g(0.762mol)胍盐酸盐溶于二甘醇，配制成1.0mol/L的溶液。将上述双(3-氨基丙基)胺均三甲苯溶液加入配有回流冷凝器及搅拌设备的反应釜中，随后加入1.1mg TBD。在氩气保护下，维持反应温度在120℃，将上述胍盐酸盐二甘醇溶液滴加进反应釜中，控制在0.5h内滴加完毕，滴加完毕后继续反应3.0h。反应完毕后，旋蒸除去溶剂，得到白色固体即为TBD盐酸盐。将TBD盐酸盐用水溶解后，加入氢氧化钠调节水溶液至pH 10，加入二氯甲烷萃取，所得二氯甲烷溶液即为TBD二氯甲烷溶液。所得TBD二氯甲烷溶液，通过旋蒸除去二氯甲烷所得白色或微黄色固体经真空干燥48h后，即得到产品TBD，产率95.0％、纯度98.0％。
实施例2
将100.0g(0.762mol)双(3-氨基丙基)胺溶于均四甲苯，配制成5.0mol/L的溶液；将58.2g(0.610mol)胍盐酸盐溶于三甘醇，配制成5.0mol/L的溶液。将上述双(3-氨基丙基)胺均四甲苯溶液加入配有回流冷凝器及搅拌设备的反应釜中，随后加入2.5mg TBD。在氩气保护下，维持反应温度在138℃，将上述胍盐酸盐三甘醇溶液滴加进反应釜中，控制在1.0h内滴加完毕，滴加完毕后继续反应4.0h。反应完毕后，旋蒸除去溶剂，得到白色固体即为TBD盐酸盐。将TBD盐酸盐用水溶解后，加入氢氧化钠调节水溶液至pH 11，加入二氯甲烷萃取，所得二氯甲烷溶液即为TBD二氯甲烷溶液。所得TBD二氯甲烷溶液，通过旋蒸除去二氯甲烷所得白色或微黄色固体经真空干燥48h后，即得到产品TBD，产率97.0％、纯度98.5％。
实施例3
将100.0g(0.762mol)双(3-氨基丙基)胺溶于均三甲苯，配制成10.0mol/L 的溶液；将87.4g(0.914mol)胍盐酸盐溶于二甘醇，配制成10.0mol/L的溶液。将上述双(3-氨基丙基)胺均三甲苯溶液加入配有回流冷凝器及搅拌设备的反应釜中，随后加入6.4mg TBD。在氩气保护下，维持反应温度在145℃，将上述胍盐酸盐二甘醇溶液滴加进反应釜中，控制在0.5h内滴加完毕，滴加完毕后继续反应4.5h。反应完毕后，旋蒸除去溶剂，得到白色固体即为TBD盐酸盐。将TBD盐酸盐用水溶解后，加入氢氧化钠调节水溶液至pH 12，加入二氯甲烷萃取，所得二氯甲烷溶液即为TBD二氯甲烷溶液。所得TBD二氯甲烷溶液，通过旋蒸除去二氯甲烷所得白色或微黄色固体经真空干燥48h后，即得到产品TBD，产率98.0％、纯度99.0％。
实施例4
将200.0g(1.524mol)双(3-氨基丙基)胺溶于均四甲苯，配制成1.0mol/L的溶液；将116.5g(1.219mol)胍盐酸盐溶于三甘醇，配制成1.0mol/L的溶液。将上述双(3-氨基丙基)胺均四甲苯溶液加入配有回流冷凝器及搅拌设备的反应釜中，随后加入8.5mg TBD。在氩气保护下，维持反应温度在145℃，将上述胍盐酸盐三甘醇溶液滴加进反应釜中，控制在1.0h内滴加完毕，滴加完毕后继续反应4.0h。反应完毕后，旋蒸除去溶剂，得到白色固体即为TBD盐酸盐。将TBD盐酸盐用水溶解后，加入氢氧化钠调节水溶液至pH 11，加入二氯甲烷萃取，所得二氯甲烷溶液即为TBD二氯甲烷溶液。所得TBD二氯甲烷溶液，通过旋蒸除去二氯甲烷所得白色或微黄色固体经真空干燥48h后，即得到产品TBD，产率98.5％、纯度99.5％。
实施例5
将200.0g(1.524mol)双(3-氨基丙基)胺溶于均三甲苯，配制成5.0mol/L的溶液；将145.6g(1.524mol)胍盐酸盐溶于二甘醇，配制成5.0mol/L的溶液。将上述双(3-氨基丙基)胺均三甲苯溶液加入配有回流冷凝器及搅拌设备的反应釜中，随后加入6.4mg TBD。在氩气保护下，维持反应温度在138℃，将上述胍盐酸盐二甘醇溶液滴加进反应釜中，控制在0.5h内滴加完毕，滴加完毕后继续反应4.5h。反应完毕后，旋蒸除去溶剂，得到白色固体即为TBD盐酸盐。将TBD盐酸盐用水溶解后，加入氢氧化钠调节水溶液至pH 10，加入二氯甲烷萃取，所得二氯甲烷溶液即为TBD二氯甲烷溶液。所得TBD二氯甲烷溶液，通过旋蒸除去二氯甲烷所得白色或微黄色固体经真空干燥48h后，即得到产品TBD，产率97.6％、纯度98.7％。
实施例6
将200.0g(1.524mol)双(3-氨基丙基)胺溶于均四甲苯，配制成10.0mol/L 的溶液；将174.7g(1.829mol)胍盐酸盐溶于三甘醇，配制成10.0mol/L的溶液。将上述双(3-氨基丙基)胺均四甲苯溶液加入配有回流冷凝器及搅拌设备的反应釜中，随后加入2.5mg TBD。在氩气保护下，维持反应温度在120℃，将上述胍盐酸盐三甘醇溶液滴加进反应釜中，控制在1.0h内滴加完毕，滴加完毕后继续反应3.0h。反应完毕后，旋蒸除去溶剂，得到白色固体即为TBD盐酸盐。将TBD盐酸盐用水溶解后，加入氢氧化钠调节水溶液至pH 12，加入二氯甲烷萃取，所得二氯甲烷溶液即为TBD二氯甲烷溶液。所得TBD二氯甲烷溶液，通过旋蒸除去二氯甲烷所得白色或微黄色固体经真空干燥24h后，即得到产品TBD，产率95.6％、纯度98.9％。
实施例7
将500.0g(3.810mol)双(3-氨基丙基)胺溶于均三甲苯，配制成1.0mol/L的溶液；将436.8g(4.572mol)胍盐酸盐溶于二甘醇，配制成1.0mol/L的溶液。将上述双(3-氨基丙基)胺均三甲苯溶液加入配有回流冷凝器及搅拌设备的反应釜中，随后加入19.1mg TBD。在氩气保护下，维持反应温度在138℃，将上述胍盐酸盐二甘醇溶液滴加进反应釜中，控制在0.5h内滴加完毕，滴加完毕后继续反应4.5h。反应完毕后，旋蒸除去溶剂，得到白色固体即为TBD盐酸盐。将TBD盐酸盐用水溶解后，加入氢氧化钠调节水溶液至pH 12，加入二氯甲烷萃取，所得二氯甲烷溶液即为TBD二氯甲烷溶液。所得TBD二氯甲烷溶液，通过旋蒸除去二氯甲烷所得白色或微黄色固体经真空干燥24h后，即得到产品TBD，产率98.7％、纯度99.1％。
实施例8
将500.0g(3.810mol)双(3-氨基丙基)胺溶于均四甲苯，配制成5.0mol/L的溶液；将364.0g(3.810mol)胍盐酸盐溶于三甘醇，配制成5.0mol/L的溶液。将上述双(3-氨基丙基)胺均四甲苯溶液加入配有回流冷凝器及搅拌设备的反应釜中，随后加入26.5mg TBD。在氩气保护下，维持反应温度在120℃，将上述胍盐酸盐三甘醇溶液滴加进反应釜中，控制在1.0h内滴加完毕，滴加完毕后继续反应4.0h。反应完毕后，旋蒸除去溶剂，得到白色固体即为TBD盐酸盐。将TBD盐酸盐用水溶解后，加入氢氧化钠调节水溶液至pH 11，加入二氯甲烷萃取，所得二氯甲烷溶液即为TBD二氯甲烷溶液。所得TBD二氯甲烷溶液，通过旋蒸除去二氯甲烷所得白色或微黄色固体经真空干燥24h后，即得到产品TBD，产率97.3％、纯度99.4％。
实施例9
将500.0g(3.810mol)双(3-氨基丙基)胺溶于均三甲苯，配制成10.0mol/L 的溶液；将291.2g(3.048mol)胍盐酸盐溶于三甘醇，配制成10.0mol/L的溶液。将上述双(3-氨基丙基)胺均三甲苯溶液加入配有回流冷凝器及搅拌设备的反应釜中，随后加入4.2mg TBD。在氩气保护下，维持反应温度在145℃，将上述胍盐酸盐三甘醇溶液滴加进反应釜中，控制在0.5h内滴加完毕，滴加完毕后继续反应3.0h。反应完毕后，旋蒸除去溶剂，得到白色固体即为TBD盐酸盐。将TBD盐酸盐用水溶解后，加入氢氧化钠调节水溶液至pH 10，加入二氯甲烷萃取，所得二氯甲烷溶液即为TBD二氯甲烷溶液。所得TBD二氯甲烷溶液，通过旋蒸除去二氯甲烷所得白色或微黄色固体经真空干燥24h后，即得到产品TBD，产率99.2％、纯度98.2％。

Claims (2)

  1. 自催化双亲混合溶剂中合成1,5,7-三氮杂双环[5.5.0]癸-5-烯(TBD)的工艺方法，以双(3-氨基丙基)胺和胍盐酸盐为原料，在亲水—疏水性双亲混合溶剂中，采用自催化法合成TBD，具体步骤如下：
    (1)将双(3-氨基丙基)胺和胍盐酸盐分别溶于疏水性溶剂和亲水性溶剂，控制各溶液浓度在1.0-10.0mol/L，控制胍盐酸盐与双(3-氨基丙基)胺的摩尔比为1：(0.8-1.2)；
    (2)将上述双(3-氨基丙基)胺溶液加入配有回流冷凝器及搅拌设备的反应釜中，随后加入占胍盐酸盐摩尔量为0.001％-0.005％的TBD作为催化剂；
    (3)在氩气保护下，维持反应温度在120-145℃，将步骤(1)配制的胍盐酸盐溶液滴加进反应釜中，控制在0.5-1.0h内滴加完毕，滴加完毕后继续反应3.0-4.5h；
    (4)反应完毕后，旋蒸除去双亲混合溶剂，得到白色固体即为TBD盐酸盐；
    (5)将TBD盐酸盐用水溶解后，加入氢氧化钠调节水溶液至pH 10-12，加入二氯甲烷萃取，所得二氯甲烷溶液即为TBD二氯甲烷溶液；
    (6)所得TBD二氯甲烷溶液，通过旋蒸除去二氯甲烷所得白色或微黄色固体经真空干燥24-48h后，即得到产品TBD，产率≥95.0％、纯度≥98.0％。
  2. 根据权利要求1所述的工艺方法，其特征在于所述亲水—疏水性双亲混合溶剂中，亲水性溶剂具体为二甘醇、三甘醇之一；疏水性溶剂具体为均三甲苯、均四甲苯之一。
PCT/CN2018/099368 2017-08-11 2018-08-08 自催化双亲混合溶剂中合成1,5,7-三氮杂双环[5.5.0]癸-5-烯的工艺方法 Ceased WO2019029561A1 (zh)

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CN107325102B (zh) * 2017-08-11 2019-11-12 南京大学 自催化双亲混合溶剂中合成1,5,7-三氮杂双环[4.4.0]癸-5-烯的工艺方法

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2011112596A2 (en) * 2010-03-10 2011-09-15 Ppg Industries Ohio, Inc. Method of making a cyclic guanidine from a guanidinium salt and a weak acid and coating compositions containing same
CN102665406A (zh) * 2009-12-24 2012-09-12 诺沃梅尔公司 合成多环胍化合物的方法
CN103172639A (zh) * 2013-03-18 2013-06-26 惠州市莱佛士制药技术有限公司 一种基于盐酸胍的六元二环胍的制备方法
CN103459393A (zh) * 2011-02-25 2013-12-18 Ppg工业俄亥俄公司 在水性介质中制备双环胍盐
CN103539798A (zh) * 2013-11-12 2014-01-29 南京大学 一种双环胍（1,5,7-三氮杂双环[5.5.0]癸-5-烯）的合成方法
CN104844608A (zh) * 2015-04-13 2015-08-19 南京大学 相转移催化法合成双环胍tbd的工艺方法
CN107325102A (zh) * 2017-08-11 2017-11-07 南京大学 自催化双亲混合溶剂中合成1,5,7‑三氮杂双环[5.5.0]癸‑5‑烯的工艺方法

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8039618B2 (en) * 2008-05-09 2011-10-18 Ppg Industries Ohio, Inc. Method for producing bicyclic guanidines by use of a cyclic urea
US8334380B2 (en) * 2008-05-09 2012-12-18 Ppg Industries Ohio, Inc. Method for producing bicyclic guanidines by use of a cyclic urea and a dehydrating agent

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102665406A (zh) * 2009-12-24 2012-09-12 诺沃梅尔公司 合成多环胍化合物的方法
WO2011112596A2 (en) * 2010-03-10 2011-09-15 Ppg Industries Ohio, Inc. Method of making a cyclic guanidine from a guanidinium salt and a weak acid and coating compositions containing same
CN103459393A (zh) * 2011-02-25 2013-12-18 Ppg工业俄亥俄公司 在水性介质中制备双环胍盐
CN103172639A (zh) * 2013-03-18 2013-06-26 惠州市莱佛士制药技术有限公司 一种基于盐酸胍的六元二环胍的制备方法
CN103539798A (zh) * 2013-11-12 2014-01-29 南京大学 一种双环胍（1,5,7-三氮杂双环[5.5.0]癸-5-烯）的合成方法
CN104844608A (zh) * 2015-04-13 2015-08-19 南京大学 相转移催化法合成双环胍tbd的工艺方法
CN107325102A (zh) * 2017-08-11 2017-11-07 南京大学 自催化双亲混合溶剂中合成1,5,7‑三氮杂双环[5.5.0]癸‑5‑烯的工艺方法

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
PHUONG-TRINH NGUYEN: "T BD-functionalized mesoporous silica: Synthesis and catalytic activity in corn oil transesterification", MICROPOROUS AND MESOPOROUS MATERIALS, vol. 180, 13 July 2013 (2013-07-13), XP028700946, ISSN: 1387-1811 *

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